Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors
IntroductionThis work outlines the design, synthesis, and biological evaluation of a new series of benzimidazole/1,2,3-triazole hybrids as apoptotic antiproliferative agents that inhibit the EGFR pathway.MethodsThe research assesses the antiproliferative efficacy of compounds 6a-i and 10a-i against...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2024.1541846/full |
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| author | Alshimaa A. Y. Ahmed Anber F. Mohammed Zainab M. Almarhoon Stefan Bräse Bahaa G. M. Youssif |
| author_facet | Alshimaa A. Y. Ahmed Anber F. Mohammed Zainab M. Almarhoon Stefan Bräse Bahaa G. M. Youssif |
| author_sort | Alshimaa A. Y. Ahmed |
| collection | DOAJ |
| description | IntroductionThis work outlines the design, synthesis, and biological evaluation of a new series of benzimidazole/1,2,3-triazole hybrids as apoptotic antiproliferative agents that inhibit the EGFR pathway.MethodsThe research assesses the antiproliferative efficacy of compounds 6a-i and 10a-i against various cancer cell lines.Results and DiscussionThe research emphasizing hybrids 6i and 10e for their remarkable activity, with GI50 values of 29 nM and 25 nM, respectively. The inhibitory effects of the most potent hybrids 6e, 6i, 10d, 10e, and 10g on EGFR were assessed. Compounds 6i and 10e exhibited greater potency than erlotinib as EGFR inhibitors. Compounds 6i and 10e were also examined for their apoptotic potential, revealing that these compounds promote apoptosis by activating caspase-3, caspase-8, and Bax, while down-regulating the anti-apoptotic protein Bcl-2. Molecular docking experiments are thoroughly examined to validate the binding interactions of the most active hybrids, 6i and 10e, with the EGFR active site. Furthermore, our new study examined the ADME properties of the new hybrids. |
| format | Article |
| id | doaj-art-c44e245a3e3f413ebd6608f981689449 |
| institution | Kabale University |
| issn | 2296-2646 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj-art-c44e245a3e3f413ebd6608f9816894492025-01-31T09:22:53ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-01-011210.3389/fchem.2024.15418461541846Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitorsAlshimaa A. Y. Ahmed0Anber F. Mohammed1Zainab M. Almarhoon2Stefan Bräse3Bahaa G. M. Youssif4Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, EgyptPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, EgyptDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaInstitute of Biological and Chemical Systems, Institute of Biological and Chemical Systems—Functional Molecular Systems, Karlsruhe Institute of Technology, Karlsruhe, GermanyPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, EgyptIntroductionThis work outlines the design, synthesis, and biological evaluation of a new series of benzimidazole/1,2,3-triazole hybrids as apoptotic antiproliferative agents that inhibit the EGFR pathway.MethodsThe research assesses the antiproliferative efficacy of compounds 6a-i and 10a-i against various cancer cell lines.Results and DiscussionThe research emphasizing hybrids 6i and 10e for their remarkable activity, with GI50 values of 29 nM and 25 nM, respectively. The inhibitory effects of the most potent hybrids 6e, 6i, 10d, 10e, and 10g on EGFR were assessed. Compounds 6i and 10e exhibited greater potency than erlotinib as EGFR inhibitors. Compounds 6i and 10e were also examined for their apoptotic potential, revealing that these compounds promote apoptosis by activating caspase-3, caspase-8, and Bax, while down-regulating the anti-apoptotic protein Bcl-2. Molecular docking experiments are thoroughly examined to validate the binding interactions of the most active hybrids, 6i and 10e, with the EGFR active site. Furthermore, our new study examined the ADME properties of the new hybrids.https://www.frontiersin.org/articles/10.3389/fchem.2024.1541846/fullbenzimidazoletriazoleEGFRapoptosiscaspases |
| spellingShingle | Alshimaa A. Y. Ahmed Anber F. Mohammed Zainab M. Almarhoon Stefan Bräse Bahaa G. M. Youssif Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors Frontiers in Chemistry benzimidazole triazole EGFR apoptosis caspases |
| title | Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors |
| title_full | Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors |
| title_fullStr | Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors |
| title_full_unstemmed | Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors |
| title_short | Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors |
| title_sort | design synthesis and apoptotic antiproliferative action of new benzimidazole 1 2 3 triazole hybrids as egfr inhibitors |
| topic | benzimidazole triazole EGFR apoptosis caspases |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2024.1541846/full |
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